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TLR3 Gene

protein-coding GIFtS: 72
GCID: GC04P186990

Toll-Like Receptor 3

See TLR3-related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Toll-Like Receptor 3¹ ²
IIAE2² ⁵
CD283²
CD283 Antigen³

External Ids:	HGNC: 11849¹	Entrez Gene: 7098²	Ensembl: ENSG00000164342⁷	OMIM: 603029⁵	UniProtKB: O15455³

Export aliases for TLR3 gene to outside databases

Previous GC identifers: GC04P188024 GC04P187670 GC04P187574 GC04P187686 GC04P187365 GC04P187227 GC04P182742

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TLR3 Gene:

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role

in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans

and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs)

that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of

effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly

expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It

recognizes dsRNA associated with viral infection, and induces the activation of NF-kappaB and the production of

type I interferons. It may thus play a role in host defense against viruses. Use of alternative polyadenylation

sites to generate different length transcripts has been noted for this gene. (provided by RefSeq, Jul 2008)

GeneCards Summary for TLR3 Gene:

TLR3 (toll-like receptor 3) is a protein-coding gene. Diseases associated with TLR3 include herpes simplex encephalitis 2, and hiv1 infection. GO annotations related to this gene include double-stranded RNA binding and receptor activity. An important paralog of this gene is ENSG00000173366.

UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455

Function: Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response

against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a

nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter

TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the

inflammatory response

summary for TLR3 Gene:

Toll-like receptors (TLRs) are single transmembrane cell-surface receptors, which have a key role in the

innate immune system. TLRs generally exist as homodimers (although TLR2-TLR6 heterodimers have been

reported) and are found on immune cells such as macrophages, B lymphocytes and mast cells. Toll-like

receptors are activated by molecules associated with biological threat and are highly specific towards

evolutionary conserved entities on microbes, such as bacterial cell-surface lipopolysaccharides, flagella

and unmethylated CpG islands. It has been suggested that some toll-like receptors may have endogenous

ligands, such as Hsp60 and fibrinogen, and this has promoted speculation that endogenous toll-like receptor

activators may have a pathological role in autoimmune disease. Activation of toll-like receptors initiates

downstream signaling cascades, initially via the adapter molecules MyD88, Trap, Trif and Tram, which

converge on the PI 3-K and NF-kappaB pathways and regulate intracellular kinases and gene expression. This

can stimulate an inflammatory and/or antigen-specific immune response. The signaling cascade coupled to

toll-like receptor activation is very similar to that of interleukin-1 receptor (IL-1R) activation.

Gene Wiki entry for TLR3 (TLR 3) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:

NC_000004.11 NT_016354.20 NC_018915.2

Regulatory elements:

Regulatory transcription factor binding sites in the TLR3 gene promoter:
AP-1 ATF-2 NF-AT NF-AT2 POU2F1 POU2F1a NF-AT3 STAT3 c-Jun NF-AT1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: TLR3 promoter sequence

Search Chromatin IP Primers for TLR3

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TLR3

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 4q35 Ensembl cytogenetic band: 4q35.1 HGNC cytogenetic band: 4q35

TLR3 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TLR3 gene location

GeneLoc information about chromosome 4 GeneLoc Exon Structure

GeneLoc location for GC04P186990: view genomic region (about GC identifiers)

Start:	186,990,306 bp from pter	End:	187,009,223 bp from pter
Size:	18,918 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455 (See protein sequence)

Recommended Name: Toll-like receptor 3 precursor

Size: 904 amino acids; 103829 Da

Subunit: Monomer and homodimer; dimerization is triggered by ligand-binding, the signaling unit is composed of one

ds-RNA of around 40 bp and two TLR3 molecules, and lateral clustering of signaling units along the length of the

ds-RNA ligand is required for TLR3 signal transduction. Interacts (via transmembrane domain) with UNC93B1; the

interaction is required for transport from the ER to the endosomes. Interacts with TICAM1 (via the TIR domain);

mediates TLR3 signaling. Interacts with SRC; upon binding of double-stranded RNA

4 PDB 3D structures from and Proteopedia for TLR3:

1ZIW (3D)

2A0Z (3D)

3ULU (3D)

3ULV (3D)

Secondary accessions: B2RAI7 E6Y0F0 E6Y0F1 Q4VAL2 Q504W0

Explore the universe of human proteins at neXtProt for TLR3: NX_O15455

Explore proteomics data for TLR3 at MOPED

Post-translational modifications:

Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding¹

TLR3 signaling requires a proteolytic cleavage mediated by cathepsins CTSB and CTSH, the cleavage occurs between

amino acids 252 and 346. The cleaved form of TLR3 is the predominant form found in endosomes¹

Glycosylation² at Asn52, Asn57, Asn70, Asn124, Asn196, Asn247, Asn252, Asn265, Asn275, Asn291,
Asn398, Asn413, Asn507, Asn636, Asn662

Modification sites at PhosphoSitePlus

See TLR3 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_003256.1

ENSEMBL proteins:

ENSP00000296795 ENSP00000423386 ENSP00000423684

Reactome Protein details: O15455

TLR3 Human Recombinant Protein Products:

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	Novus Biologicals TLR3 Proteins Novus Biologicals TLR3 Lysate
	Sino Biological Recombinant Protein for TLR3 Sino Biological Cell Lysate for TLR3
	Browse ProSpec Recombinant Proteins
	Cloud-Clone Corp. Proteins for TLR3
	Search eBioscience for Proteins for TLR3
	antibodies-online proteins for TLR3 (14 products)
	antibodies-online peptides for TLR3

TLR3 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of TLR3
	R&D Systems Antibodies for TLR3
	Cell Signaling Technology (CST) Antibodies for TLR3
	OriGene Antibodies for TLR3 OriGene Custom Antibody Services for TLR3
	Novus Biologicals TLR3 Antibodies
	Abcam antibodies for TLR3
	Cloud-Clone Corp. Antibodies for TLR3
	ThermoFisher Antibody for TLR3
	antibodies-online antibodies for TLR3 (211 products)

TLR3 Assay Products:

	Browse Kits and Assays available from EMD Millipore
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	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for TLR3
	Browse Enzo Life Sciences for kits & assays
	Cloud-Clone Corp. ELISAs for TLR3 Cloud-Clone Corp. CLIAs for TLR3
	Search eBioscience for ELISAs for TLR3
	antibodies-online kits for TLR3 (23 products)

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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HGNC Gene Families:

CD: CD molecules

IUPHAR Guide to PHARMACOLOGY protein family classification: TLR3

Toll-like receptor family

Selected InterPro protein domains (see all 6):

IPR000483 Cys-rich_flank_reg_C

IPR000372 LRR-contain_N

IPR001611 Leu-rich_rpt

IPR000157 TIR_dom

IPR027173 TLR3

Graphical View of Domain Structure for InterPro Entry O15455

ProtoNet protein and cluster: O15455

4 Blocks protein domains:

IPB000157 TIR domain

IPB000372 Cysteine-rich flanking region

IPB000483 Cysteine-rich flanking region

IPB001611 Leucine-rich repeat signature

UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455

Domain: ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18

Similarity: Belongs to the Toll-like receptor family

Similarity: Contains 22 LRR (leucine-rich) repeats

Similarity: Contains 1 LRRCT domain

Similarity: Contains 1 LRRNT domain

Similarity: Contains 1 TIR domain

Find genes that share domains with TLR3 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: TLR3_HUMAN, O15455

Function: Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response

against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a

nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter

TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the

inflammatory response

Genatlas biochemistry entry for TLR3:

Drosophila transmembrane receptor Toll homolog 3,with the major transcripts,predominantly expressed in placenta

and pancreas,involved in immune defense

Gene Ontology (GO): 4 molecular function terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003725	double-stranded RNA binding	NAS	12054664
GO:0004872	receptor activity	TAS	10426995
GO:0004888	transmembrane signaling receptor activity	NAS	12054664
GO:0005515	protein binding	IPI	16858407

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Phenotypes:
12 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for Tlr3):

behavior/neurological	cardiovascular system	endocrine/exocrine gland	hematopoietic system	homeostasis/metabolism
immune system	mortality/aging	muscle	nervous system	reproductive system
respiratory system	tumorigenesis

Find genes that share phenotypes with TLR3 About GenesLikeMe

Animal Models:
MGI mouse knock-outs for TLR3: Tlr3^tm1Flv Tlr3^tm1Ttg

genOway: Develop your customized and physiologically relevant rodent model for TLR3

miRNA Products:		miRTarBase miRNAs that target TLR3: hsa-mir-124-3p (MIRT022528)

		Block miRNA regulation of human, mouse, rat TLR3 using miScript Target Protectors
		Search for qRT-PCR Assays for microRNAs that regulate TLR3
		SwitchGear 3'UTR luciferase reporter plasmid: TLR3 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for TLR3
		Predesigned siRNA for gene silencing in human, mouse, rat TLR3

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for TLR3

Clone Products:		OriGene clones in human, mouse for TLR3 (see all 6) OriGene ORF clones in mouse, rat for TLR3 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: TLR3 (NM_003265)
		Sino Biological Human cDNA Clone for TLR3
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TLR3
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TLR3
		Addgene plasmids for TLR3

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for TLR3
		Browse ESI BIO Cell Lines and PureStem Progenitors for TLR3

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TLR3

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

TLR3_HUMAN, O15455: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome membrane

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
endoplasmic reticulum	5
endosome	5
golgi apparatus	4
lysosome	4
plasma membrane	4
vacuole	4
nucleus	3
extracellular	2
peroxisome	2
cytosol	1
mitochondrion	1

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Gene Ontology (GO): Selected cellular component terms (see all 11): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000139	Golgi membrane	TAS	--
GO:0005622	intracellular	--	--
GO:0005737	cytoplasm	IDA	19740627
GO:0005765	lysosomal membrane	IDA	17897319
GO:0005789	endoplasmic reticulum membrane	TAS	--

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(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for TLR3 About (see all 19)

See pathways by source

Powered
by

SuperPath

Contained pathways About

Toll-like receptor signaling pathway

	Toll-like receptor signaling pathway	0.94			Regulation of toll-like receptor signaling pathway	0.93
	Toll-like receptor signaling pathway	0.94			Hepatitis B	0.31

NOD-like Receptor Signaling Pathways

	NOD-like Receptor Signaling Pathways	0.58			Inflammasome Activation Pathways	0.51
	Toll-Like receptor Signaling Pathways	0.58			Immune response TLR3 and TLR4 induce TICAM1-specific signaling pathway	0.32

Cytosolic sensors of pathogen-associated DNA

	RIP-mediated NFkB activation via ZBP1	0.81			Cytosolic sensors of pathogen-associated DNA	0.38
	ZBP1(DAI) mediated induction of type I IFNs	0.81

Toll Like Receptor 7/8 (TLR7/8) Cascade

	MyD88-independent cascade	0.69			TRIF-mediated programmed cell death	0.00
	Toll Like Receptor 3 (TLR3) Cascade	0.69

NF-KappaB Family Pathway

NF-KappaB (p50-p65) Pathway

0.72

NF-KappaB Family Pathway

0.72

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Pathways by source See SuperPaths
Show all pathways

Selected R&D Systems Pathways for TLR3 (see all 6)

	NOD-like Receptor Signaling Pathways
	Inflammasome Activation Pathways
	IL-21 Signaling and its Primary Biological Effects in Different Immune Cell Types
	Th1 Differentiation
	Toll-Like receptor Signaling Pathways

Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for TLR3 (see all 9)

	NF-KappaB (p50-p65) Pathway
	Toll-Like Receptors Pathway
	TRAF Pathway
	TREM1 Pathway
	Colorectal Cancer Metastasis

1 Cell Signaling Technology (CST) Pathway for TLR3

NF-kappaB Signaling

1 Tocris Bioscience Pathway for TLR3

Toll-like Receptor Pathway

1 GeneGo (Thomson Reuters) Pathway for TLR3

Immune response TLR3 and TLR4 induce TICAM1-specific signaling pathway

2 BioSystems Pathways for TLR3

	Toll-like receptor signaling pathway
	Regulation of toll-like receptor signaling pathway

1 Sino Biological Pathway for TLR3

NF-kB (NFkB) Pathway

Selected Reactome Pathways for TLR3 (see all 8)

	TRIF-mediated programmed cell death
	IKK complex recruitment mediated by RIP1
	Toll Like Receptor 3 (TLR3) Cascade
	MyD88-independent cascade
	Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon

5 Kegg Pathways (Kegg details for TLR3):

	Toll-like receptor signaling pathway
	Hepatitis C
	Hepatitis B
	Influenza A
	Herpes simplex infection

Pathway & Disease-focused RT² Profiler PCR Arrays including TLR3 (see all 8):

Antiviral Response in human mouse rat

Toll-Like Receptor Signaling Pathway in human mouse rat

Inflammatory Response & Autoimmunity in human mouse rat

Inflammatory Response & Autoimmunity 384HT in human mouse rat

Innate & Adaptive Immune Responses in human mouse rat

Interactions:

GeneGlobe Interaction Network for TLR3

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for TLR3 (O15455^{1, 2, 3} ENSP00000296795⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 75)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
PIK3R1	P27986¹^,²^,³, ENSP00000274335⁴	EBI-6289595,EBI-79464 MINT-2840093 MINT-2840114 I2D: score=2 STRING: ENSP00000274335
ENSG00000184494	Q99519³	I2D: score=1
ENSG00000223957	Q99519³	I2D: score=1
ENSG00000227129	Q99519³	I2D: score=1
ENSG00000227315	Q99519³	I2D: score=1

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Gene Ontology (GO): Selected biological process terms (see all 52): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001934	positive regulation of protein phosphorylation	--	--
GO:0002224	toll-like receptor signaling pathway	TAS	--
GO:0002282	microglial cell activation involved in immune response	IEA	--
GO:0002756	MyD88-independent toll-like receptor signaling pathway	TAS	--
GO:0006952	defense response	--	--

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Enzo Life Sciences drugs & compounds for TLR3

Browse compounds at ApexBio

Compounds for TLR3 available from Tocris Bioscience About this table

Compound	Action	CAS #
Pam2CSK4	TLR2/6 agonist; induces TNF-alpha production	[868247-72-7]
Resiquimod	Toll-like receptor 7 (TLR7) agonist	[144875-48-9]
Pam3CSK4	TLR1/2 agonist; induces cytokine production	[112208-00-1]
Poly(I:C)	TLR3 agonist	[42424-50-0]
Imiquimod	Toll-like receptor 7 (TLR7) agonist	[99011-02-6]

1 IUPHAR Ligand for TLR3 (TLR3) About this table

Ligand	Type	Action	Affinity	Pubmed IDs
polyIC	Agonist	Agonist		11607032

Selected Novoseek inferred chemical compound relationships for TLR3 gene (see all 22) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
poly(i-c)	92.4	66	16384532 (3), 15845391 (3), 16142732 (3), 14688319 (2) (see all 38)
polyinosinic-polycytidylic acid	92.1	72	17962643 (4), 19452017 (4), 19154402 (2), 18949355 (2) (see all 36)
flagellin	77	14	16365459 (1), 19294011 (1), 19955831 (1), 19740321 (1) (see all 14)
inosine monophosphate	74.2	13	17182588 (3), 17573354 (1), 18715647 (1), 15196204 (1) (see all 11)
peptidoglycan	68.8	16	16365459 (1), 17114468 (1), 16670332 (1), 14996826 (1) (see all 12)
rantes	67.9	14	19121387 (3), 19452017 (2), 16436653 (1), 14517278 (1) (see all 9)
lipoteichoic acid	58.1	4	17114468 (1), 15652398 (1), 16052591 (1), 16175622 (1)
tab-2	52.8	3	14982987 (2), 12609980 (1)
2',5'-oligoadenylate	52.8	2	17669408 (1)
imiquimod	51.6	2	19578865 (1), 19643938 (1)

1 PharmGKB related drug/compound annotation for TLR3 gene About this table

Drug/compound	PharmGKB Annotation
Measles vaccines	CA

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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for TLR3 gene:

NM_003265.2

Unigene Cluster for TLR3:

Toll-like receptor 3

Hs.657724 [show with all ESTs]

Unigene Representative Sequence: BC068487

5 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000296795(uc003iyq.3) ENST00000513189 ENST00000512264(uc011ckz.2 uc003iyr.3)

ENST00000504367 ENST00000508051

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		Predesigned siRNA for gene silencing in human, mouse, rat TLR3

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		GenScript: all cDNA clones in your preferred vector: TLR3 (NM_003265)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TLR3
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TLR3
		Addgene plasmids for TLR3

Primer Products:		OriGene qPCR primer pairs and template standards for TLR3 OriGene qSTAR qPCR primer pairs in human, mouse for TLR3
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat TLR3
		QuantiTect SYBR Green Assays in human, mouse, rat TLR3
		QuantiFast Probe-based Assays in human, mouse, rat TLR3

Additional mRNA sequence:

AB445631.1 AK302143.1 AK314208.1 BC017954.1 BC043204.2 BC059372.1 BC068487.1 BC094737.1

BC096333.1 BC096334.3 BC096335.1 DQ445682.1 DQ470075.1 DQ470076.1 DQ470077.1 DQ470078.1

DQ470079.1 U88879.1

4 DOTS entries:

DT.109361 DT.100664575 DT.101977909 DT.99984982

Selected AceView cDNA sequences (see all 50):

BQ007482 CF529473 AU135937 NM_003265 BC068487 CF528559 BX104394 BI489939

CD109430 BF594247 BC059372 CB960574 BU624267 AL048899 CF994731 BX489678

BU929797 BU853465 CB989983 BF971051 BX489646 U88879 BG573455 BX495055

GeneLoc Exon Structure

3 Alternative Splicing Database (ASD) splice patterns (SP) for TLR3 About this scheme

ExUns:	1	^	2	^	3	^	4a	·	4b	^	5a	·	5b	·	5c	^	6
SP1:							-		-
SP2:									-
SP3:

ECgene alternative splicing isoforms for TLR3

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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TLR3 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: CACTCTGTTT

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TLR3 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 5) fully expand


Blood (Cardiovascular System)
Conventional Dendritic Cells I Spleen

Spleen (Hematopoietic System)
Conventional Dendritic Cells I Spleen

Skeletal Muscle (Muscoskeletal System) fully expand to see all 2 entries
Muscle Progenitor Cells Mandibular Arch Muscles

Epithelial Cells
Outer Root Sheath Cells Outer Root Sheath

Hair (Integumentary System)
Outer Root Sheath Cells Outer Root Sheath

TLR3 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

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TLR3 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.657724

UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455

Tissue specificity: Expressed at high level in placenta and pancreas. Also detected in CD11c+ immature dendritic

cells. Only expressed in dendritic cells and not in other leukocytes, including monocyte precursors. TLR3 is the

TLR that is expressed most strongly in the brain, especially in astrocytes, glia, and neurons

Pathway & Disease-focused RT² Profiler PCR Arrays including TLR3 (see all 8):

Antiviral Response in human mouse rat

Toll-Like Receptor Signaling Pathway in human mouse rat

Inflammatory Response & Autoimmunity in human mouse rat

Inflammatory Response & Autoimmunity 384HT in human mouse rat

Innate & Adaptive Immune Responses in human mouse rat

Primer Products:		OriGene qPCR primer pairs and template standards for TLR3 OriGene qSTAR qPCR primer pairs in human, mouse for TLR3
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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of animals.

Orthologs for TLR3 gene from Selected species (see all 14) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Tlr3^{1 , 5}	toll-like receptor 3^{1, 5}	81.31(n)¹ 79.93(a)¹		8 (25.31 cM)⁵ 142980¹ NM_126166.4¹ NP_569054.2¹ 45395665⁵
chicken (Gallus gallus)	Aves	TLR3¹	toll-like receptor 3	66.82(n) 61.8(a)		422720 NM_001011691.3 NP_001011691.3
lizard (Anolis carolinensis)	Reptilia	TLR3⁶	toll-like receptor 3	57(a)	1 ↔ 1	5(112305568-112319535)
tropical clawed frog (Xenopus tropicalis)	Amphibia	tlr3¹	toll-like receptor 3	59.31(n) 55.86(a)		100486223 XM_002934402.2 XP_002934448.2
zebrafish (Danio rerio)	Actinopterygii	tlr3¹	toll-like receptor 3	52.99(n) 49.2(a)		403126 NM_001013269.3 NP_001013287.2
fruit fly (Drosophila melanogaster)	Insecta	CG9562³ Tollo¹	Tollo¹	26(a) (best of 2)³ 42.12(n)¹ 30.79(a)¹		44497¹ NM_080018.2¹ NP_524757.1¹

ENSEMBL Gene Tree for TLR3 (if available)
TreeFam Gene Tree for TLR3 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for TLR3 gene

ENSG00000173366² CD180² TLR7² TLR1² TLR9² TLR5² TLR10² TLR4²

TLR8² TLR6² TLR2²

1 SIMAP similar gene for TLR3 using alignment to 4 protein entries: TLR3_HUMAN (see all proteins):

TLR2

Find genes that share paralogs with TLR3 About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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Polymorphic Variants from UniProtKB/Swiss-Prot

TLR3_HUMAN, O15455: The Phe-412 allele (dbSNP:rs3775291) occurs with a frequency of 30% in populations with European and

Asian ancestry, and confers some natural resistance to HIV-1 infection

SNP ID	Valid	Clinical significance	Chr 4 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
VAR_054887⁴		Herpes simplex encephalitis 2 (HSE2)⁴	--	see VAR_054887	2	P S	mis⁴		0	--	--	--	--
rs121434431^1,2	C,F	other¹	186763303(+)	`GTGGTC/TCCATT`	2	P S	mis¹		1		NA	4550
rs36027624^1,2	C	--	182754573(+)	`AAAAA-/A/AA AAAAA`	1	--	int¹		2		NA CSA	4
rs115313599^1,2	C,F	--	186747149(+)	`GGACTC/GAAGTG`	1	--	us2k¹		1		WA	118
rs139507674^1,2		--	186747253(+)	`ACCACA/GTTGCC`	1	--	us2k¹		0	--	--	--	--
rs145586023^1,2		--	186747290(+)	`AAGCAA/GTCTCC`	1	--	us2k¹		0	--	--	--	--
rs75217467^1,2	C,F	--	186747300(+)	`CTAAAG/ATGTTG`	1	--	us2k¹		2		CSA WA	120
rs182928749^1,2		--	186747430(+)	`AATGTA/GCAGTA`	1	--	us2k¹		0	--	--	--	--
rs147725378^1,2		--	186747470(+)	`AACTAA/GCAAGA`	1	--	us2k¹		0	--	--	--	--
rs187045018^1,2		--	186747588(+)	`AAGTCA/GTGGGA`	1	--	us2k¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for TLR3 (186990306 - 187009223 bp)

Structural Variations
Database of Genomic Variants (DGV) 6 variations for TLR3: About this table

Variant ID	Type	Subtype	PubMed ID
esv2677545	CNV	Deletion	23128226
dgv683n27	CNV	Gain	19166990
nsv470097	CNV	Gain	18288195
dgv5852n71	CNV	Gain	21882294
nsv881424	CNV	Gain	21882294
dgv5851n71	CNV	Gain	21882294

Human Gene Mutation Database (HGMD): TLR3

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing TLR3

DNA2.0 Custom Variant and Variant Library Synthesis for TLR3

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 603029
OMIM disorders: 613002 609423
UniProtKB/Swiss-Prot: TLR3_HUMAN, O15455

Herpes simplex encephalitis 2 (HSE2) [MIM:613002]: A rare complication of human herpesvirus 1 (HHV-1)

infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic

necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache,

seizures, stupor, and often coma, frequently with a fatal outcome. Note=Disease susceptibility is associated with

variations affecting the gene represented in this entry. TLR3 mutations predispose otherwise healthy individuals

to isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced

immune defense against viral infection in the central nervous system

19 diseases for TLR3:
About MalaCards

herpes simplex encephalitis 2 hiv1 infection hiv-1 herpes simplex encephalitis

encephalitis pouchitis acquired immunodeficiency syndrome herpes simplex

measles corneal disease hiv/aids hiv-1 viremia

tick-borne encephalitis herpes simplex encephalitis 1 west nile virus rapid progression to aids from hiv1 infection

aids, rapid progression to aids, slow progression to aids, delayed/rapid progression to

5 inferred disease relationships from the University of Copenhagen DISEASES database for TLR3:

Encephalitis Melanoma Influenza Herpes simplex

Asthma

Find genes that share disorders with TLR3 About GenesLikeMe

Selected Novoseek inferred disease relationships for TLR3 gene (see all 29) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
virus infection	73.1	57	16877304 (2), 14575692 (2), 19452017 (2), 12672806 (2) (see all 36)
inflammation	48.6	13	19752565 (2), 20387535 (2), 18403353 (1), 20483774 (1) (see all 9)
hepatitis c chronic	38.3	1	19475618 (1)
necrosis	32.7	9	14729660 (1), 15579900 (1), 16510559 (1), 18765427 (1) (see all 9)
melanoma	32.1	27	17671143 (4), 19001446 (3), 19470740 (2), 17142768 (1) (see all 14)
hepatitis c	30.8	3	19625408 (2), 18021446 (1)
influenza	30.4	10	15579900 (3), 19231996 (3), 16399790 (2), 16517210 (1) (see all 5)
bacterial infections	27.2	1	18083507 (1)
herpes simplex	23.9	3	19025601 (1), 16847112 (1)
pouchitis	20.9	3	16770571 (2)

Genetic Association Database (GAD): TLR3
Human Genome Epidemiology (HuGE) Navigator: TLR3 (55 documents)

Export disorders for TLR3 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for TLR3 gene, integrated from 10 sources (see all 684):
(articles sorted by number of sources associating them with TLR3)

Utopia: connect your pdf to the dynamic
world of online information

Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. (PubMed id 18753640)^{1, 2, 4, 9} Yang Z.... Zhang K. (N. Engl. J. Med. 2008)
A family of human receptors structurally related to Drosophila Toll. (PubMed id 9435236)^{1, 2, 3} Rock F.L.... Bazan J.F. (Proc. Natl. Acad. Sci. U.S.A. 1998)
TLR3 gene polymorphisms and liver disease manifestations in chronic hepatitis C. (PubMed id 19475618)^{1, 4, 9} Askar E....Mihm S. (J. Med. Virol. 2009)
Investigation of the [-/A]8 and C1236T genetic variations within the human Toll-like receptor 3 gene for association with multiple sclerosis. (PubMed id 20483009)^{1, 4, 9} Szvetko A.L....Griffiths L.R. (Neurol. Res. 2010)
Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. (PubMed id 15961631)^{1, 2, 9} Choe J.... Wilson I.A. (Science 2005)
Single-nucleotide polymorphisms in genes encoding toll-like receptor -2, -3, -4, and -9 in case-control study with breast cancer. (PubMed id 19810822)^{1, 4, 9} Etokebe G.E....DembiA8 Z. (Genet Test Mol Biomarkers 2009)
Toll-like receptor polymorphisms and age-related macular degeneration. (PubMed id 18385087)^{1, 4, 9} Edwards A.O....Tosakulwong N. (amp 2008)
Polymorphisms in toll-like receptor 4 and toll-like receptor 9 influence viral load in a seroincident cohort of HIV-1-infected individuals. (PubMed id 19855253)^{1, 4, 9} Pine S.O....Bochud P.Y. (AIDS 2009)
Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation. (PubMed id 18946062)^{1, 4, 9} Bochud P.Y....Boeckh M. (N. Engl. J. Med. 2008)
Innate immunity of the ocular surface and ocular surface inflammatory disorders. (PubMed id 18813073)^{1, 4, 9} Ueta M. (Cornea 2008)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 7098	HGNC: 11849	AceView: TLR3	Ensembl:ENSG00000164342	euGenes: HUgn7098
ECgene: TLR3	Kegg: 7098	H-InvDB: TLR3

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for TLR3	Pharmacogenomics, SNPs, Pathways
TLR3base	http://bioinf.uta.fi/TLR3base/

Intellectual Property for TLR3 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for TLR3 gene:
Search GeneIP for patents involving TLR3

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, eBioscience, antibodies-online, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
Advanced Cell Diagnostics, Animal models from genOway)
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